Accuracy of needle placement is a matter of fundamental importance in brain interventions such as tumor surgery and deep brain stimulation (DBS), and there is a need for improvements in order to increase efficacy of treatment. In response to this need, we have developed a computer-controlled system designed to steer a flexible needle through brain tissue, with proportional control of steering angle, using an elegantly simple technique of slowly rotating the needle in a duty-cycled fashion during insertion. The system can be used to reach targets deep in the brain, and can detour when needed in order to avoid damaging sensitive areas. Preliminary testing of the system has been performed in vitro in a gelatin substrate and in human cadavers. The testing that has been performed to date on this technology has focused solely on efficacy in reaching a particular target. There remain several unanswered needs, especially the development of means for tracking the tip of the flexible probe in vivo. However, before progressing to these questions, research is needed in several areas in order to ensure the safety of the technique. The specific aims of this proposal are as follows: 1. To adapt the tip geometry and the velocity envelope for safety in brain parenchyma. This will require finite element modeling of the needle tip geometry and the process of needle rotation in order to optimize the material, bevel angle, edge sharpness, rotation speed, and insertion speed of the probe in order to avoid damage to tissue. Results of the work will be validated in fresh animal brain tissue in vitro and then in vivo. 2. To adapt the tip geometry and the velocity envelope for safety in contact with blood vessels. This aim will involve testing in vivo in a porcine model, with comparisons to standard straight-sided biopsy needles, in order to validate the needle geometry, rotation speed, and insertion speed of the probe, to avoid damage to blood vessels that are contacted during insertion. The goal will be to limit the amount of bleeding detected via CT to that exhibited by present clinical straight-probe brain needle designs. 3. To optimize the design and the velocity envelope to avoid tissue damage along the length of the curved needle trajectory. Unlike a straight probe, insertion of a flexible needle of course places a certain amount of stress along the outer curvature of the needle path. Therefore, in addition to the above work dealing specifically with the needle tip, it will be necessary to model the interaction between the flexible needle and the tissue all along the shaft, optimizing the design of the needle gauge and the velocity envelope to avoid tissue damage along the trajectory. This work will also serve to prevent the possibility of any whirling or whipping motion of the tip of the flexible needle as the shaft is rotated. This work will be validated in animal tissue in vitro and then in a porcine model in vivo. These aims are expected to result in a needle tip that looks less like a bevel-tipped needle and more like a round-tipped needle with the high point of the round tip shifted off-center. PUBLIC HEALTH RELEVANCE: This research involves the development of improved techniques for reaching treatment sites deep in the brain, while causing minimal disturbance to surrounding healthy parts of the brain. It has the potential to improve treatment outcomes for cancer, Parkinson's disease, and other disorders.